PrP cooperates with STI1 to regulate SOD activity in PrP-deficient neuronal cell line
PrP cooperates with STI1 to regulate SOD activity in PrP-deficient neuronal cell line
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DOI：
10.1016/j.bbrc.2004.12.132
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发表时间：
2005-03-04
影响因子：
3.1
通讯作者：
Onodera, T
中科院分区：
文献类型：
--
作者：
Sakudo, A;Lee, DC;Onodera, T
细胞朊蛋白（PrPc）在血清剥夺诱导的永生化朊蛋白基因（Prnp）缺陷神经元细胞凋亡中起抗凋亡和抗氧化作用。PrPc的八肽重复区（OR）和N端半个疏水区（HR）是PrPc活性不可缺少的部分，但其作用机制尚不清楚。在本研究中，阐明的机制，其中PrPC eltered的抗氧化活性是促进应激诱导蛋白1（STI 1）介导的PrPC依赖的超氧化物歧化酶（SOD）激活的证据。免疫沉淀显示PrPc与STI 1相关。针对PrPc-STI 1结合的抑制肽[STI 1 pep. 1和PrP（113-132）]对PrPC表达细胞的毒性作用是通过抑制SOD活性，而对Prnp（-/-）细胞无毒性作用。此外，OR和HR的N端一半是PrP（113-132）而不是STI 1 pep的抑制作用所必需的。1.这些数据是一致的结果建立了一个模型，其中OR和N-末端一半的HR介导的作用，STI 1后细胞存活和SOD活性的上调。(C)2004年爱思唯尔公司All rights reserved.
Cellular prion protein (PrPc) plays anti-apoptotic and anti-oxidative roles in apoptosis induced by serum deprivation in an immortalized prion protein gene (Prnp)-deficient neuronal cell line. The octapeptide repeat region (OR) and N-terminal half of the hydrophobic region (HR) of PrPc are indispensable for PrPc activity, but the mechanisms remain unclear. In the present study, elucidation of the mechanisms by which PrPC elicits the anti-oxidative activities was facilitated by evidence of stress-inducible protein 1 (STI1) mediating PrPC-dependent superoxide dismutase (SOD) activation. Immunoprecipitation revealed that PrPc was associated with STI1. The inhibitory peptides against PrPc-STI1 binding [STI1 pep. 1 and PrP (113-132)] indicated toxic activity in PrPC-expressing cells by inhibiting SOD activity but not in Prnp(-/-) cells. Furthermore, OR and N-terminal half of the HR were required for the inhibitory effect of PrP ( 113-132) but not STI1 pep. 1. These data are consistent with results established with a model where OR and N-terminal half of the HR mediate the action of STI1 upon cell survival and upregulation of SOD activity. (C) 2004 Elsevier Inc. All rights reserved.